The proposal reflects the interest of this laboratory in reflex patterning in different states of CNS excitation as a major factor in organization of vertebrate behavior. The neural agent of biting reflexes in sharks, the mesencephalic trigeminal (Mes V) complex is included in a circumventricular organ (CVO) - a special evolutionary adaptation of the Mes V in sharks. The clustered primary sensory neurons of the Mes V may act as a biological amplifier for reflex biting, so that small sensory signals from the mouth region may produce large, synchronous discharges to the jaw muscles and powerful biting. The siting of the Mes V primary sensory neurons in a CVO strongly suggests modulation of Mes V amplifier functions by a) neural input from other brain areas; b) chemicals (e.g., hormones) secreted into the blood at sites distant to the Mes V; c) chemicals (monoamines, peptides) secreted into the cerebrospinal fluid (CSF) by a population of intra-CSF axon terminals in possible nonsynaptic relationship to an immediately adjacent population of large Mes V neurons residing in the CSF compartment; d) chemicals (e.g, steroids, peptides) released into the CSF compartment from afar. The shark Mes V complex offers opportunities to study: 1) the apparently unprecedented control of primary sensory neurons of a major reflex system by the combined neural-neuroendocrine activities of a CVO; 2) the important hypothesis of nonsynaptic transmission/modulation in the vertebrate CNS; 3) the general manner of CVO operation in a model system whose unusual properties offer unusual research opportunities. To these ends we propose a number of specific tasks. 1. Ultrastructural analysis (correlative SEM/TEMO the sub- and supraependymal neuronal, glial, ependymal and vascular elements of the Mes V CVO and their interrelationships. 2. Experimental analysis of the blood-brain and CSF-brain barriers of the CVO, using light and TEM microscopy with HRP tracing. 3. Tracing the origins of intra-CSF axonal terminals with HRP and light microscopy. 4. Measurement of the normal monoamine pattern of the Mes V CVO (and other brain areas) in several species of sharks, using HPLC with electrodetection. 5. Identification of monoamine-bearing neural elements of the Mes V CVO using the methods of immunocytochemistry.